IL-10 is required for regulatory T cells to mediate tolerance to alloantigens in vivo

M Hara, CI Kingsley, M Niimi, S Read… - The Journal of …, 2001 - journals.aai.org
M Hara, CI Kingsley, M Niimi, S Read, SE Turvey, AR Bushell, PJ Morris, F Powrie, KJ Wood
The Journal of Immunology, 2001journals.aai.org
We present evidence that donor-reactive CD4+ T cells present in mice tolerant to donor
alloantigens are phenotypically and functionally heterogeneous. CD4+ T cells contained
within the CD45RB high fraction remained capable of mediating graft rejection when
transferred to donor alloantigen-grafted T cell-depleted mice. In contrast, the CD45RB low
CD4+ and CD25+ CD4+ populations failed to induce rejection, but rather, were able to
inhibit rejection initiated by naive CD45RB high CD4+ T cells. Analysis of the mechanism of …
Abstract
We present evidence that donor-reactive CD4+ T cells present in mice tolerant to donor alloantigens are phenotypically and functionally heterogeneous. CD4+ T cells contained within the CD45RB high fraction remained capable of mediating graft rejection when transferred to donor alloantigen-grafted T cell-depleted mice. In contrast, the CD45RB low CD4+ and CD25+ CD4+ populations failed to induce rejection, but rather, were able to inhibit rejection initiated by naive CD45RB high CD4+ T cells. Analysis of the mechanism of immunoregulation transferred by CD45RB low CD4+ T cells in vivo revealed that it was donor Ag specific and could be inhibited by neutralizing Abs reactive with IL-10, but not IL-4. CD45RB low CD4+ T cells from tolerant mice were also immune suppressive in vitro, as coculture of these cells with naive CD45RB high CD4+ T cells inhibited proliferation and Th1 cytokine production in response to donor alloantigens presented via the indirect pathway. These results demonstrate that alloantigen-specific regulatory T cells contained within the CD45RB low CD4+ T cell population are responsible for the maintenance of tolerance to donor alloantigens in vivo and require IL-10 for functional activity.
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